The encoding, storage, retrieval and[unreadable] consolidation of either episodic or other forms of memory involves temporally[unreadable] extended interactions of large neural populations distributed over multiple[unreadable] brain regions. We propose to conduct a neurophysiological analysis of[unreadable] memory-related neural ensemble interactions within a closely linked system of[unreadable] brain regions that are important in mnemonic processes. These regions include[unreadable] hippocampus, amygdala, medial prefrontal cortex, dorsal and ventral striatum[unreadable] and substantia nigra/ventral tegmentum. Our main focus is the process of[unreadable] spontaneous memory trace reactivation, operationally defined in[unreadable] neurophysiological terms as the reestablishment of neural activity patterns[unreadable] that match those that were imposed by recent experience. Retrieval of sequences[unreadable] of such previously encoded patterns can be understood as a neural reflection of[unreadable] episodic memory. Off-line retrieval has long been proposed to assist in the[unreadable] process of memory consolidation. Previously, we established several important[unreadable] basic characteristics of this process: it occurs coherently among hippocampal[unreadable] and some neocortical neural ensembles; it recreates, in a compressed form, the[unreadable] short-term temporal order of encoded experiences; it is strongest during a[unreadable] period of 30-60 minutes after an experience, but can be observed at least 24[unreadable] hours later. Of particular importance for this proposal is our observation that[unreadable] hippocampal memory trace reactivation is expressed primarily during a specific[unreadable] neurophysiological event, the hippocampal sharp-wave. Sharp-waves have been[unreadable] proposed on theoretical grounds to reflect the convergence of hippocampal[unreadable] associative networks onto attractor (i.e., stored memory) states. This proposal[unreadable] addresses a number of key unanswered questions: Is reactivation of memory[unreadable] traces in neocortical and subcortical structures coordinated by the[unreadable] hippocampus? Is there a window of enhanced neocortical or subcortical[unreadable] plasticity during sharp-waves? Is hippocampal reactivation dependent on NMDA[unreadable] receptor activation during encoding? Is the reactivation process potentiated by[unreadable] positive or negative reinforcement and does it interact with the firing of[unreadable] dopamine neurons in a manner that may assist in learning routes to reward? Do[unreadable] localized drug applications (e.g., in the hippocampus or amygdala), which[unreadable] facilitate or impair memory consolidation, affect the reactivation process?[unreadable] Such analyses require large scale parallel recording methods, and we have[unreadable] developed technology that will enable simultaneous recording from about 150-200[unreadable] single neurons distributed over multiple structures in unanesthetized, behaving[unreadable] rodents. These studies should clarify the neurophysiological mechanisms of[unreadable] memory retrieval and consolidation, and assist in understanding deficits in[unreadable] this process that occur under conditions such as normal and pathological aging,[unreadable] brain trauma, developmental disorders and substance abuse.